1. Field of the Invention
The present invention relates generally to the fields of pharmaceutical chemistry and formulation. More particularly, it concerns the use of an effective amount of riboflavin and amino acids, in any combination, in the alleviation of the nutritional, metabolic and toxic symptoms of cancer and cancer chemotherapy in diagnosed cancer patients.
2. Description of the Related Art
In spite of the progress which has been made over the years in the areas of cytotoxic chemotherapy, immunotherapy, and radiation therapy in the treatment of patients with a variety of malignant and nonmalignant disorders, most of the commonly used antineoplastic drugs produce immediate toxicities in the organs composed of self-renewing cell populations such as the gastrointestinal tract epithelium. As a result, many patients suffer such toxic effects as pancytopenia, alopecia, nausea and vomiting, as well as a variety of other physical distresses. In fact, it has been shown in numerous studies (Vachon, M. L. S. et al., J. Pain Symptom Management, 10, 142-150 (1995); Coyle, N. et al., J. Pain Symptom Management, 5, 83-93 (1990)) that outside of pain, the most common symptoms reported by patients diagnosed with cancer and/or undergoing chemotherapy treatment for cancer are fatigue, weakness, and appetite disturbances, the latter of which directly contributes to the other symptoms.
Moreover, these symptoms are so common that they are frequently neglected by physicians, and patients may be told that there is nothing that can be done to remedy these side-effects. In some patients, correction of anemia, reduced concentrations of sodium, potassium, calcium, and glucose in the blood, dehydration, and enhanced function of major organs may provide a relief. Adjustment of the dosages of medications, which may contribute to fatigue and weakness, including analgesics, muscle relaxants, and anti-depressants may also provide temporary relief. Pharmacological management of fatigue includes the use of psychostimulatory agents such as methylphenidate, pemoline and corticosteroids, as described by Brietbart, W. et al. (Psychosomatics, 33, 352-356 (1992)) Unfortunately, in most patients such measures are short-lasting or not effective.
When total parenteral nutrition (TPN) was introduced, it was speculated that improvement of the patient's nutrition would treat several emergency situations related to cancer and the side effects of therapy, as well as reduce weakness and tiredness. Unfortunately, this was not observed in most cancer patients receiving TPN, and the efficacy of TPN to improve patient nutritional status and survival remains questionable (Koretz, R. L. J. Clinical Oncology, 2: 534-538 (1984); McGeer, A. J.; Detsky, A. S.; O'Rourke, K. Ann. Internal Med., 110: 734-736 (1989)). A variety of studies have been conducted since the inception of TPN, with an array of conflicting reports. In some of them, TPN facilitated cancer progression through supply of large quantities of nutrients necessary for cancer growth, suggesting that the broad use of TPN in cancer patients could be deleterious at worst or ineffective at best. While it has been clearly shown that exogenous substrates have a distinct effect on both host and cancer metabolism, the characteristics of the substrates, such as caloric intake and the kind of amino acids used appear to be crucial for a selective response. As a result, fatigue and weakness are currently not indicators for the use of TPN in cancer patients.
In spite of such seemingly conflicting reports, several amino acids have indicated promise as nutritional supplements in the treatment of a variety of disorders, including cancer. Key amongst these are arginine, glycine, ornithine and taurine. The amino acid arginine has properties which suggest that it may be of value both nutritionally and immunologically when administered as a dietary supplement. In fact, research has shown that a retardation in tumor growth, tumor regression, decreased tumor incidence, or a combination of all three can be affected by the administration of dietary arginine. Additionally, mixtures which contain arginine as well as a variety of other amino acids, sugars, vitamins, and nucleobases have exhibited potentially cytotoxic effects against several cancer cell lines. The non-essential amino-acid glycine has been shown to inhibit hepatocyte proliferation, and may have general anticancer properties as a dietary supplement.
In addition to amino acids, a variety of vitamins and their analogs have been tested for potential cancer therapeutic effects as part of TPN regimens, but for the most part the results have been inadequate to confirm or deny the benefits, and the evidence relating to cancer is weak or conflicting. However, several vitamins, most notably Vitamins A, B, C, and D have shown preliminary promise for use in cancer therapy.
There accordingly exists a need for a process to alleviate the side effects of cytotoxicity associated with cancer and cancer chemotherapy, specifically a decrease of fatigue and weakness, an increase of energy, and the reduction of toxicity of chemotherapy regimens. Simultaneously, improving the nutritional status of cancer patients unlikely to have a curative response to existing therapeutic regimens has potential for decreasing the size of the tumors within the patient.